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Summary: Background: There is a scarcity of published studies evaluating transgender/gender‐diverse youth before initiating gender‐affirming hormones. Aim: To study the body composition, metabolic syndrome (MetS) components and lifestyle habits in treatment‐naïve transgender youth. Methods: Cross‐sectional study evaluating 153 transgender youth [median age 15.7 years, 94 transgender males] who attended The Israeli Children and Adolescents Gender Clinic between 6/2021–12/2022. Clinical, metabolic data and lifestyle habits (diet, physical activity and sleep patterns) were retrieved from the medical files. Body composition was determined by bioelectrical impedance analysis. Body mass index and muscle‐to‐fat ratio z‐scores were calculated by sex designated at birth. Results: Weight categories differed between genders, with a greater proportion of subjects classified as underweight among transgender females, and a greater proportion affected by overweight/obese/severe obese among transgender males (p = 0.035). The odds for MetS components were increased by 2.2 for every 1 standard deviation decrease in the muscle‐to‐fat ratio z‐score (95%CI: 1.45 to 3.26, p < 0.001). About one‐third of the cohort did not meet any of the three lifestyle recommendations. Transgender males had increased odds for MetS components by 3.49 (95%CI: 1.63 to 7.44, p = 0.001). Conclusions: Treatment‐naïve transgender‐male adolescents have an imbalance between muscle and adipose tissue, which places them at increased susceptibility for MetS components even prior to hormonal treatment. [ABSTRACT FROM AUTHOR]

Introduction: X-linked hypophosphatemia (XLH) is caused by an inactivating mutation in the phosphate-regulating endopeptidase X-linked (PHEX) gene whose defective product fails to control phosphatonin fibroblast growth factor 23 (FGF23) serum levels. Although elevated FGF23 levels have been linked with detrimental cardiac effects, the cardiologic outcomes in XLH patients have been subject to debate. Our study aimed to evaluate the prevalence and severity of cardiovascular morbidity in pediatric XLH patients before, during, and after a 2- year treatment period with burosumab, a recombinant anti-FGF23 antibody Methods: This prospective observational study was conducted in a tertiary medical center, and included 13 individuals with XLH (age range 0.6--16.2 years) who received burosumab every 2 weeks. Clinical assessment at treatment initiation and after .5, 1, and 2 years of uninterrupted treatment included anthropometric measurements and cardiologic evaluations (blood pressure [BP], electrocardiogram, conventional echocardiography, and myocardial strain imaging). Results: The linear growth of all patients improved significantly (mean height zscore: from -1.70 ± 0.80 to -0.96 ± 1.08, P=0.03). Other favorable effects were decline in overweight/obesity rates (from 46.2% to 23.1%) and decreased rates of elevated BP (systolic BP from 38.5% to 15.4%; diastolic BP from 38.5% to 23.1%). Electrocardiograms revealed no significant abnormality throughout the study period. Cardiac dimensions and myocardial strain parameters were within the normative range for age at baseline and remained unchanged during the study period. Conclusion: Cardiologic evaluations provided reassurance that 2 years of burosumab therapy did not cause cardiac morbidity. The beneficial effect of this treatment was a reduction in cardiovascular risk factors, as evidenced by the lower prevalence of both overweight/obesity and elevated BP. [ABSTRACT FROM AUTHOR]

Background: Graves' disease has been associated with adverse pregnancy, labor and delivery, and neonatal outcomes. Thyroid function levels, assessed during newborn screening (NBS), can serve as indicators of the adaptation in the hypothalamic–pituitary–thyroid axis. We utilized data from the national thyroid NBS program to investigate the characteristics of the mother–infant dyad of term infants born to mothers with past or active Graves' disease. Methods: The dataset of the Israeli NBS for thyroid function was linked with the electronic records of a tertiary medical center to generate a unified database of mothers and their term infants born between 2011 and 2021. The MDClone big data platform extracted maternal, pregnancy, disease course, labor and delivery, and neonatal characteristics of the mother-infant dyads. Results: Out of 103,899 registered mother–infant dyads, 292 (0.3%) mothers had past or active Graves' disease. A forward multivariate linear regression demonstrated that Graves' disease did not significantly affect NBS total thyroxine (tT4) levels (p = 0.252). NBS tT4 levels in infants born to mothers with active Graves' disease were higher than those observed in the general Israeli population (p < 0.001). Mothers with Graves' disease more frequently used assisted reproductive technology (12.7% vs. 9.0%, respectively, p = 0.012; odds ratio [OR] = 1.46 [CI 1.03–2.07], p = 0.031), and had more gestational hypertension (3.9% vs. 1.1%, p < 0.001; OR = 3.53 [CI 1.92–6.47], p < 0.001), proteinuria (2.5% vs. 0.9%, p < 0.001; OR = 3.03 [CI 1.43–6.45], p = 0.004), cesarean sections (26.4% vs. 19.7%, p = 0.029; OR = 1.46 [CI 1.13–1.90], p = 0.004), prelabor rupture of membranes (15.4% vs. 4.1%, p < 0.001; OR = 4.3 [CI 3.13–5.91], p < 0.001), and placental abnormalities (5.1% vs. 2.0%, p < 0.001; OR = 2.64 [CI 1.57–4.44]; p < 0.001). Their infants had lower adjusted birthweight z-scores (−0.18 ± 0.94 vs. −0.03 ± 0.90, p = 0.007) and were more likely to be small for gestational age (12.0% vs. 8.1%, p = 0.005; OR = 1.54 [CI 1.08–2.19], p = 0.018). Conclusions: Neonatal thyroid function levels were affected by maternal Graves' disease only when the disease was active during gestation. Moreover, maternal Graves' disease was also associated with an increased risk of adverse outcomes for the mother–infant dyad. [ABSTRACT FROM AUTHOR]

Background: Women with type 1 diabetes (T1D) are more susceptible than men to cardiovascular disease (CVD). Signs of increased risk may already appear among adolescent girls. Objectives: We explored the contribution of body composition to the development of CVD risk factors among youth with T1D. Methods: One hundred and eighty nine subjects with T1D (mean age 15.3 ± 5.1 years, 55% boys) followed between January 2018–January 2022 were included in this observational study. Sociodemographic and clinical data were extracted from medical files. Body composition was measured by bioelectrical impedance analysis, and muscle‐to‐fat ratio (MFR) z‐scores were calculated. Logistic regression model assessed the association between body composition (MFR z‐scores) and evidence of CVD risk factors. Results: Females were characterised by higher median BMI z‐scores (0.47 vs. 0.04, p = 0.012), higher fat and truncal fat percentage levels (p ≤ 0.001) and lower median MFR z‐scores (−0.64 vs. −0.25, p ≤ 0.001), higher median triglyceride (TG) levels (71 vs. 61 mg/dl, p = 0.05), longer disease duration to initiation of insulin pump therapy (p = 0.041), and more time spent in marked hypoglycemia (1 vs. 0.2%, p = 0.007) than males. Males' MFR z‐scores were associated with several diabetes‐related parameters (age at diagnosis, CGM metrics, HbA1c and insulin dose), while the females'' MFR z‐scores were linked to the atherogenic dyslipidemia index (TG:HDL ratio). The odds for CVD risk factors were doubled for every 1 SD decrease in MFR z‐score (OR = 0.50, CI [0.30–0.84], p = 0.009) and also increased with age (OR = 1.07, CI [1.004–1.148], p = 0.038). Conclusions: Body composition measurement has a predictive value in CVD risk assessment in youth with T1D, with unique characteristics and influences in each sex. [ABSTRACT FROM AUTHOR]